tbuckley/cabot-search huggingface dataset:
Sex and gender in COPD and asthma
Authors: Joan B. Soriano, Francesca Polverino
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Sex is a paramount part of overall health. Respirologists and primary care doctors, when dealing with respiratory patients and aiming for holistic management, should not consider sexual health a taboo.</b>https://bit.ly/3trQZaq
Reply: The concept and application of the treatable traits approach in interstitial lung disease and other chronic respiratory diseases
Authors: Yet H. Khor, Christopher J. Ryerson
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Acute exacerbation is a key adverse outcome of ILD, with different associated factors that are treatable traits. The interdisciplinary geriatric evaluation can support development of the treatable traits approach for chronic respiratory diseases.</b>https://bit.ly/46qXmtb
Reversing Resistance of Cancer Stem Cells and Enhancing Photodynamic Therapy Based on Hyaluronic Acid Nanomicelles for Preventing Cancer Recurrence and Metastasis
Authors: Teng Wang, Jiaojiao Tao, Bingjie Wang, Tianze Jiang, Xia Zhao, Yang Yu, Xin Meng
Journal: Advanced Healthcare Materials (2023)

Abstract Photodynamic therapy (PDT) is a promising approach for tumor treatment; however, the therapeutic resistance of cancer stem cells (CSCs) severely limits its efficacy and easily lead to recurrence. Herein, a hyaluronic acid (HA)‐Ce6‐Olaparib (OLA) micelle (HCCO) is developed, which combines the CSC targeting of HA, the PDT effect of Ce6, and the DNA damage repair inhibition of OLA. More importantly, HCCO induces immunogenic cell death (ICD) effects, promotes dendritic cells maturation, and alleviates myeloid‐derived suppressor cells (MDSCs) infiltration to reverse CSC resistance. As a result, HCCO not only significantly inhibits the growth of 4T1 breast cancer cells and CSCs in vitro, but also effectively inhibits tumor recurrence and metastasis in vivo. This study provides a novel strategy for preventing tumor recurrence and metastasis by the combination of inhibiting DNA damage repair, reversing CSC resistance, and enhancing PDT.
Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer’s disease
Authors: Hyunkyung Mo, Juryun Kim, Jennifer Yejean Kim, Jang Woon Kim, Heeju Han, Si Hwa Choi, Yeri Alice Rim, Ji Hyeon Ju
Journal: Translational Neurodegeneration (2023)

Abstract Background Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly, resulting in gradual destruction of cognitive abilities. Research on the development of various AD treatments is underway; however, no definitive treatment has been developed yet. Herein, we present induced pluripotent stem cell (iPSC)-derived cortical neural stem cell secretome (CNSC-SE) as a new treatment candidate for AD and explore its efficacy. Methods We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation. Then to confirm the efficacy in vivo, CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity (5 μg/g, once a week, 4 weeks). The cell-mediated effects on nerve recovery, amyloid beta (Aβ) plaque aggregation, microglial and astrocyte detection in the brain, and neuroinflammatory responses were investigated. Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects. Results Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro. Furthermore, CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts. The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβ plaque accumulation. Conclusions Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential, non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.
Prehospital high-dose methylprednisolone in resuscitated out-of-hospital cardiac arrest patients (STEROHCA): a randomized clinical trial
Authors: Laust E R Obling, Rasmus P Beske, Martin A S Meyer, Johannes Grand, Sebastian Wiberg, Benjamin Nyholm, Jakob Josiassen, Frederik T Søndergaard, Thomas Mohr, Anders Damm-Hejmdal, Mette Bjerre, Ruth Frikke-Schmidt, Fredrik Folke, Jacob E Møller, Jesper Kjaergaard, Christian Hassager
Journal: Intensive Care Medicine (2023)

Patients who are successfully resuscitated following out-of-hospital cardiac arrest (OHCA) are still at a high risk of neurological damage and death. Inflammation and brain injury are components of the post-cardiac arrest syndrome, and can be assessed by systemic interleukin 6 (IL-6) and neuron-specific enolase (NSE). Anti-inflammatory treatment with methylprednisolone may dampen inflammation, thereby improving outcome. This study aimed to determine if prehospital high-dose methylprednisolone could reduce IL-6 and NSE in comatose OHCA patients. The STEROHCA trial was a randomized, blinded, placebo-controlled, phase II prehospital trial performed at two cardiac arrest centers in Denmark. Resuscitated comatose patients with suspected cardiac etiology were randomly assigned 1:1 to a single intravenous injection of 250 mg methylprednisolone or placebo. The co-primary outcome was reduction of IL-6 and NSE-blood levels measured daily for 72 h from admission. The main secondary outcome was survival at 180 days follow-up. We randomized 137 patients to methylprednisolone (n = 68) or placebo (n = 69). We found reduced IL-6 levels (p < 0.0001) in the intervention group, with median (interquartile range, IQR) levels at 24 h of 2.1 pg/ml (1.0; 7.1) and 30.7 pg/ml (14.2; 59) in the placebo group. We observed no difference between groups in NSE levels (p = 0.22), with levels at 48 h of 18.8 ug/L (14.4; 24.6) and 14.8 ug/L (11.2; 19.4) in the intervention and placebo group, respectively. In the intervention group, 51 (75%) patients survived and 44 (64%) in the placebo group. Prehospital treatment with high-dose methylprednisolone to resuscitated comatose OHCA patients, resulted in reduced IL-6 levels after 24 h, but did not reduce NSE levels.
Adult Mental Health, Substance Use Disorders, and Functional Outcomes of Children Resilient to Early Adversity
Authors: William E. Copeland, Julia Halvorson-Phelan, Ellen McGinnis, Lilly Shanahan
Journal: American Journal of Psychiatry (2023)

Some children are unaffected by mental illness despite exposure to childhood adversity. These children are typically considered resilient. The objective of this study was to follow up such resilient children in adulthood to characterize mental health status, substance use, and functional outcomes.
Racial and Ethnic Disparities in COVID-19-Related Stressor Exposure and Adverse Mental Health Outcomes Among Health Care Workers
Authors: Aaron Samuel Breslow, Sherry Simkovic, Peter J. Franz, Elizabeth Cavic, Qi Liu, Natalie Ramsey, Jonathan E. Alpert, Benjamin Le Cook, Vilma Gabbay
Journal: American Journal of Psychiatry (2023)

Racial and ethnic disparities in exposure to COVID-19-related stressors, pandemic-related distress, and adverse mental health outcomes were assessed among health care workers in the Bronx, New York, during the first wave of the pandemic.
Role of intravenous ketamine in the pathogenesis of secondary sclerosing cholangitis in critically ill patients: perpetrator or innocent bystander? Answers provided by forensic toxicology
Authors: Silke Leonhardt, Sven Baumann, Christian Jürgensen, Lars Hüter, Julia Leonhardt, Lisa Höfert, Michael Bauer, Frank Tacke
Journal: Intensive Care Medicine (2023)
LIES of omission: complex observation processes in ecology
Authors: Fergus J. Chadwick, Daniel T. Haydon, Dirk Husmeier, Otso Ovaskainen, Jason Matthiopoulos
Journal: Trends in Ecology & Evolution (2023)

Advances in statistics mean that it is now possible to tackle increasingly sophisticated observation processes. The intricacies and ambitious scale of modern data collection techniques mean that this is now essential. Methodological research to make inference about the biological process while accounting for the observation process has expanded dramatically, but solutions are often presented in field-specific terms, limiting our ability to identify commonalities between methods. We suggest a typology of observation processes that could improve translation between fields and aid methodological synthesis. We propose the LIES framework (defining observation processes in terms of issues of Latency, Identifiability, Effort and Scale) and illustrate its use with both simple examples and more complex case studies.
Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases
Authors: Ze-Qin Wen, Jun Lin, Wen-Qing Xie, Yun-Han Shan, Ge-Hua Zhen, Yu-Sheng Li
Journal: Military Medical Research (2023)

Degenerative musculoskeletal diseases are structural and functional failures of the musculoskeletal system, including osteoarthritis, osteoporosis, intervertebral disc degeneration (IVDD), and sarcopenia. As the global population ages, degenerative musculoskeletal diseases are becoming more prevalent. However, the pathogenesis of degenerative musculoskeletal diseases is not fully understood. Previous studies have revealed that endoplasmic reticulum (ER) stress is a stress response that occurs when impairment of the protein folding capacity of the ER leads to the accumulation of misfolded or unfolded proteins in the ER, contributing to degenerative musculoskeletal diseases. By affecting cartilage degeneration, synovitis, meniscal lesion, subchondral bone remodeling of osteoarthritis, bone remodeling and angiogenesis of osteoporosis, nucleus pulposus degeneration, annulus fibrosus rupture, cartilaginous endplate degeneration of IVDD, and sarcopenia, ER stress is involved in the pathogenesis of degenerative musculoskeletal diseases. Preclinical studies have found that regulation of ER stress can delay the progression of multiple degenerative musculoskeletal diseases. These pilot studies provide foundations for further evaluation of the feasibility, efficacy, and safety of ER stress modulators in the treatment of musculoskeletal degenerative diseases in clinical trials. In this review, we have integrated up-to-date research findings of ER stress into the pathogenesis of degenerative musculoskeletal diseases. In a future perspective, we have also discussed possible directions of ER stress in the investigation of degenerative musculoskeletal disease, potential therapeutic strategies for degenerative musculoskeletal diseases using ER stress modulators, as well as underlying challenges and obstacles in bench-to-beside research.
Lebrikizumab improved itch and reduced the extent of itch interference on sleep in patients with moderate-to-severe atopic dermatitis: two randomized, placebo-controlled, phase III trials
Authors: Gil Yosipovitch, Peter A Lio, David Rosmarin, Esther Serra-Baldrich, Franz J Legat, Marta Casillas, Evangeline Pierce, Zhuqing Liu, Luna Sun, Hany Elmaraghy, Sonja Ständer
Journal: British Journal of Dermatology (2023)

Itch and sleep loss due to itch are prevalent symptoms of moderate-to-severe atopic dermatitis, significantly impairing patients’ quality of life and wellbeing. First-line topical therapy is insufficient for most patients and there is an unmet need for effective treatments that provide symptom relief and quality of life improvement. In two randomized, placebo-controlled, phase III trials, significantly more patients treated with the novel monoclonal antibody lebrikizumab had ≥ 3-point improvement in Pruritus Numeric Rating Scale by week 16 vs. patients treated with placebo. In addition, significantly more patients treated with lebrikizumab achieved ≥ 1-point improvement in Sleep-Loss Scale score by week 16 vs. placebo. Onset of itch relief was rapid, occurring within the first few days of treatment.
Precipitous changes in nomenclature and definitions—NAFLD becomes SLD: Implications for and expectations of AASLD journals
Authors: Harmeet Malhi, Robert S. Brown, Joseph K. Lim, Nancy Reau, Elliot B. Tapper, Carmen Chak-Lui Wong, Gregory J. Gores
Journal: Hepatology (2023)

Malhi, Harmeet; Brown, Robert S. Jr; Lim, Joseph K.; Reau, Nancy; Tapper, Elliot B.; Wong, Carmen Chak-Lui; Gores, Gregory J. Author Information
The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3–SRF axis
Authors: Xiaoxuan Zhong, Xiang Wei, Yan Xu, Xuehai Zhu, Bo Huo, Xian Guo, Gaoke Feng, Zihao Zhang, Xin Feng, Zemin Fang, Yuxuan Luo, Xin Yi, Ding-Sheng Jiang
Journal: Acta Pharmaceutica Sinica B (2023)

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
Functional profiling of gut microbial and immune responses toward different types of dietary fiber: a step toward personalized dietary interventions
Authors: Jian Tan, Rosilene V. Ribeiro, Christopher Barker, Claire Daien, Erick De Abreu Silveira, Andrew Holmes, Ralph Nanan, Stephen J. Simpson, Laurence Macia
Journal: Gut Microbes (2023)

Dietary fiber plays a crucial role in maintaining gut and overall health. The objective of this study was to investigate whether different types of dietary fiber elicited specific changes in gut microbiota composition and the production of short-chain fatty acids. To test this, a longitudinal crossover study design was employed, in which healthy adult women consumed three distinct dietary fiber supplements: Inulin (fructo-oligosaccharide), Vitafiber (isomalto-oligosaccharide), and Fibremax (mixture of different fiber) during a one-week intervention period, followed by a 2-week washout period. A total of 15 g of soluble fiber was consumed daily for each supplement. Samples were collected before and after each intervention to analyze the composition of the gut microbiota by 16S rRNA sequencing and fecal levels of short-chain fatty acids measured using nuclear magnetic resonance. Phenotypic changes in peripheral blood mononuclear cells were studied in subsets of participants with higher SCFA levels post-intervention using spectral flow cytometry. The results revealed substantial stability and resilience of the overall gut bacterial community toward fiber-induced changes. However, each supplement had specific effects on gut bacterial alpha and beta diversity, SCFA production, and immune changes. Inulin consistently exerted the most pronounced effect across individuals and certain taxa were identified as potential indicators of SCFA production in response to inulin supplementation. This distinguishing feature was not observed for the other fiber supplements. Further large-scale studies are required to confirm these findings. Overall, our study implies that personalized dietary fiber intervention could be tailored to promote the growth of beneficial bacteria to maximize SCFA production and associated health benefits.
“Mesenchymal stromal (stem) cell therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury.” C.C. dos Santos, H. Amatullah, C.M. Vaswani,<i>et al. Eur Respir J</i>2022; 59: 2004216.
Journal: European Respiratory Journal (2023)

Unfortunately, an error was made in labelling figure 2m of this manuscript.The labels on the horizontal axis underneath the chart should have been labelled as "NC" (negative control), "INH" (miR-193b-5p inhibitor), and "TNF" (tumour necrosis factor), but the second of these was labelled as "MIM" in error, instead of "INH".The corrected version of figure 2 is shown below.
GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer
Authors: Qiwei Jiang, Yong Li, Songwang Cai, Xingyuan Shi, Yang Yang, Zihao Xing, Zhenjie He, Shengte Wang, Yubin Su, Meiwan Chen, Zhesheng Chen, Zhi Shi
Journal: Acta Pharmaceutica Sinica B (2023)

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.
In Vitro Mechanical Stimulation to Reproduce the Pathological Hallmarks of Human Cardiac Fibrosis on a Beating Chip and Predict The Efficacy of Drugs and Advanced Therapies
Authors: Roberta Visone, Camilla Paoletti, Alessandro Cordiale, Letizia Nicoletti, Carla Divieto, Marco Rasponi, Valeria Chiono, Paola Occhetta
Journal: Advanced Healthcare Materials (2023)

Abstract Cardiac fibrosis is one of the main causes of heart failure, significantly contributing to mortality. The discovery and development of effective therapies able to heal fibrotic pathological symptoms thus remain of paramount importance. Micro‐physiological systems (MPS) are recently introduced as promising platforms able to accelerate this finding. Here a 3D in vitro model of human cardiac fibrosis, named uScar, is developed by imposing a cyclic mechanical stimulation to human atrial cardiac fibroblasts (AHCFs) cultured in a 3D beating heart‐on‐chip and exploited to screen drugs and advanced therapeutics. The sole provision of a cyclic 10% uniaxial strain at 1 Hz to the microtissues is sufficient to trigger fibrotic traits, inducing a consistent fibroblast‐to‐myofibroblast transition and an enhanced expression and production of extracellular matrix (ECM) proteins. Standard of care anti‐fibrotic drugs (i.e., Pirfenidone and Tranilast) are confirmed to be efficient in preventing the onset of fibrotic traits in uScar. Conversely, the mechanical stimulation applied to the microtissues limit the ability of a miRNA therapy to directly reprogram fibroblasts into cardiomyocytes (CMs), despite its proved efficacy in 2D models. Such results demonstrate the importance of incorporating in vivo‐like stimulations to generate more representative 3D in vitro models able to predict the efficacy of therapies in patients.
Treatable traits: the added value of comprehensive geriatric assessment
Authors: Simone Scarlata, Panaiotis Finamore, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The identification of "treatable traits" in interstitial lung disease, as well as in chronic airway diseases, involves a thorough patient evaluation and comprehensive geriatric assessment represents the ideal tool for achieving this goal</b>https://bit.ly/3E6x3vF
Astrocytes and microglia-targeted Danshensu liposomes enhance the therapeutic effects on cerebral ischemia-reperfusion injury
Authors: Min Bai, Na Cui, Yucheng Liao, Chao Guo, Liang Li, Ying Yin, Aidong Wen, Jingwen Wang, Weiliang Ye, Yi Ding
Journal: Journal of Controlled Release (2023)
TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas
Authors: Jiaying Zheng, Lingxiao Wang, Shunyi Zhao, Wenjing Zhang, Yuzhou Chang, Dale B Bosco, Tao Huang, Aastha Dheer, Shan Gao, Shengze Xu, Katayoun Ayasoufi, Rawan Al-Kharboosh, Fangfang Qi, Manling Xie, Aaron J Johnson, Haidong Dong, Alfredo Quiñones-Hinojosa, Long-Jun Wu
Journal: Neuro-Oncology (2023)

Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors.